Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

AIMS: Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation, and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB. METHODS AND RESULTS: In 11 sedated spontaneously breathing pigs, obstructive apnoeas were simulated by 75 s of intermittent negative upper airway pressure (INAP) applied by a negative pressure device connected to the endotracheal tube. Intermittent negative upper airway pressures were performed before and after PVI. AF-inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by programmed atrial stimulation. Pulmonary vein isolation prolonged the aERP by 48 ± 27 ms in the right atrium (RA) (P < 0.0001) and by 40 ± 34 ms in the left atrium (LA) (P = 0.0004). Following PVI, AF-inducibility dropped from 28 ± 26% to 0% (P = 0.0009). Intermittent negative upper airway pressure was associated with a transient aERP-shortening (ΔaERP) in both atria, which was not prevented by PVI (INAP indued ΔaERP after PVI in the RA: -57 ± 34 ms, P = 0.0002; in the LA: -42 ± 24 ms, P < 0.0001). Intermittent negative upper airway pressure was associated with a transient increase in AF-inducibility (from 28 ± 26% to 69 ± 21%; P = 0.0008), which was not attenuated by PVI [INAP-associated AF-inducibility after PVI: 58 ± 33% (P = 0.5)]. CONCLUSION: Transient atrial arrhythmogenic changes related to acute obstructive respiratory events are not prevented by electrical isolation of the pulmonary veins, which partially explains the increased AF recurrence in patients with SDB after PVI procedures.

Pathophysiological mechanisms and treatment strategies in atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF reduces the patients' quality of life and increases the risks of heart failure, ischaemic stroke, and death. The aetiology of AF is complex and involves multiple pathophysiological pathways. Comorbidities often coexist in patients with AF and contribute to the pathogenesis. The pathogenesis, the most common comorbidities, and possible individualized treatment options of AF are discussed in this review.

Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial.

BACKGROUND: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. METHODS: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. DISCUSSION: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.

3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide.

Aim: To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs. Materials and methods: Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination. Results: We present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2-4 individual veins as well as 1-2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered. Conclusion: Fluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.

Imaging approaches for pulmonary vein isolation in patients after lobectomy or pneumonectomy: a case series.

Background: In patients who underwent pneumonectomy, pulmonary vein isolation for atrial fibrillation by catheter ablation may be complicated by the anatomical alterations caused by the surgical intervention. Pre- and peri-procedural imaging can visualize and guide the procedure to assure safety and procedural success. Case summary: This case series describes different imaging and ablation strategies in three cases from three different ablation centres with the unusually challenging and complex anatomical conditions in patients following lobectomy or pneumonectomy. Discussion: Pulmonary vein isolation in patients with previous pulmonary resection was feasible by both radiofrequency and cryocatheter ablation despite the anatomical alterations caused by the surgery. Pre- and peri-procedural imaging by cardiac computed tomography and transoesophageal echocardiography contributed to an increased understanding of the complex anatomical substrate.

Recurring episodes of bundle branch reentry ventricular tachycardia due to aortitis preceded by SARS-CoV-2 infection: a case report.

BACKGROUND: SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2-5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. CASE PRESENTATION: A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. CONCLUSION: We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option.

Validation of the national Danish ablation database: a retrospective, registry-based validation study.

Aim.To validate the National Danish Ablation Database (NDAD) by investigating to what extent data in NDAD correspond to medical records.Type of study. Non-blinded, registry-based, retrospective, validation study. Material and methods. A sample of patients who underwent ablation for atrial fibrillation in Denmark between 1 January 2016 and 31 December 2016 were included. By utilizing medical records as gold standard, positive predictive (PPV) and negative predictive values (NPV) for NDAD were assessed and presented as five main categories: arrhythmia characteristics, demographics, cardiac history, complications, and medication. PPV's and NPV's exceeding 90% were considered as high agreement. Results. 597 patients (71.0% males) were included in the study. Median age was 63.1 (IQR: 54.9-68.4) years. The median PPV and NPV estimates across all variables were respectively 90.4% (95% CI: 68%-95.2%) (PPV) and 99.4% (95% CI: 98.4%-99.8%) (NPV) at baseline, and 91.7% (95% CI: 67.4%-95.4%) (PPV) and 99.3% (98.2%-99.3%) (NPV) at follow-up. Conclusion. The data registered in NDAD agrees to a great extent with the patients' medical records, suggesting NDAD is a database with high validity. As a result of low complication rate, the PPV- and NPV-estimates among complication variables were prone to somewhat greater uncertainty compared to the rest.

Periprocedural complications and one-year outcomes after catheter ablation for treatment of atrial fibrillation in elderly patients: a nationwide Danish cohort study.

OBJECTIVES: To investigate complications within 30-days following first-time ablation for atrial fibrillation (AF), including a composite of cardiac tamponade, hematoma requiring intervention, stroke or death, in patients ≥ 75 years of age, compared to patients aged 65-74 years. In addition, one-year all-cause mortality and AF relapse were compared. METHODS & RESULTS: All patients receiving their first catheter ablation for AF between 2012 and 2016 were identified using Danish nationwide registries. Patients aged 65-74 years served as the reference group for patients ≥ 75 years. Relapse of AF within one year was defined as cardioversion following a three-month blanking period, re-ablation or confirmed relapse within follow-up. The composite complication outcome did not differ between the two age groups, with 39/1554 (2.8%) in patients 65-74 years of age, versus 5/199 (2.5%) in older patients (adjusted HR = 0.94), 95% CI: 0.37-2.39, P = 0.896). Patients ≥ 75 years or older had no increased hazard of death within 30 days after the procedure, with an incidence of 3/1554 (0.2%) in younger patients and 2/199 (1.0%) in patients ≥ 75 years of age (adjusted HR = 4.71, 95% CI: 0.78-28.40, P = 0.091). There was no difference in relapse of AF after one year between age groups (≥ 75 years adjusted HR = 1.00, 95% CI: 0.78-1.26, P = 0.969). CONCLUSION: In patients ≥ 75 years of age selected for catheter ablation for AF, the incidence of periprocedural complications, as well as one-year freedom from AF showed no statistical difference, when compared to patients 65-74 years of age.

Lenient rate control versus strict rate control for atrial fibrillation: a protocol for the Danish Atrial Fibrillation (DanAF) randomised clinical trial.

INTRODUCTION: Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation. METHODS AND ANALYSIS: We plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation. ETHICS AND DISSEMINATION: Ethics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04542785.

Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation.

BACKGROUND: Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. METHODS AND RESULTS: The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1-Q3]=1.6-4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1-Q3=319-1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1-Q3=62-1026) in patients with and 77 (Q1-Q3=24-448) in patients without recurrence of AF (P=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26-6.43), P=0.01. CONCLUSIONS: This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACRTN12606000467538.

Massive electrical storm at disease onset in a patient with Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a genetic arrhythmogenic disease characterized by ST-segment elevations in the right precordial leads of the electrocardiogram (ECG). These ECG changes may be concealed and BrS may present with electrical storm characterized by recurrent ventricular tachycardia and fibrillation. CASE REPORT: A 49-year-old previously healthy man was admitted with electrical storm. The patient received direct current (DC) cardioversion shocks and only after intravenous lidocaine did the electrical storm slowly subside with a total of 255 DC shocks administered during the first 24 h after admission. He fully recovered and received an implantable cardioverter-defibrillator. Subsequent drug challenge with flecainide revealed type 1 BrS. CONCLUSIONS: Massive electrical storm can be the first symptom of BrS and the diagnostic ECG changes may be concealed at presentation. Although hundreds of DC shocks may be required during initial treatment, full recovery can be achieved.

The predictive value of CHADS2 risk score in post myocardial infarction arrhythmias - a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy.

BACKGROUND: Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose of this study was to investigate if CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI. METHODS: The study included 297 post-MI patients from the CARISMA study with left ventricular ejection fraction (LVEF) ≤40%. All patients were implanted with an implantable cardiac monitor (ICM) within 5 to 21 days post-MI and followed every three months for two years. Atrial fibrillation, bradyarrhythmias and ventricular tachycardias were diagnosed using the ICM, pacemaker or ICD. Patients were stratified according to CHADS2 score at enrollment. Congestive heart failure was defined as LVEF ≤40% and NYHA class II, III or IV. RESULTS: We found significantly increased risk of an arrhythmic event with increasing CHADS2 score (CHADS2 score=1-2: HR=2.1 [1.1-3.9], p=0.021, CHADS2 score ≥ 3: HR=3.7 [1.9-7.1], p<0.001). This pattern was identical when dividing the arrhythmias into subgroups of atrial fibrillation, ventricular tachycardias and bradyarrhythmias. CHADS2 score was similarly associated with the development of major cardiovascular events defined as reinfarction, stroke, and hospitalization for heart failure or cardiovascular death. CONCLUSION: In the post-MI setting, CHADS2 score efficiently identifies populations at high risk for cardiac arrhythmias.

New-onset atrial fibrillation predicts malignant arrhythmias in post-myocardial infarction patients--a Cardiac Arrhythmias and RIsk Stratification after acute Myocardial infarction (CARISMA) substudy.

BACKGROUND: After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial. OBJECTIVE: The purpose of this study was to investigate if new-onset atrial fibrillation (AF) is associated with development of potential malignant brady- and tachyarrhythmias after an acute MI. METHODS: The study included 277 post-MI patients from the CARISMA study with left ventricular ejection fraction ≤ 40%, New York Heart Association class I, II, or III and no history of AF. All patients were implanted with an implantable cardiac monitor within 4 to 27 days after an acute MI and followed every 3 months for 2 years. Time-dependent association between new-onset AF > 30 s and the development of bradyarrhythmias and/or ventricular tachyarrhythmias were investigated using Cox proportional hazard regressions. RESULTS: New-onset AF was associated with an increased risk of bradyarrhythmias when adjusting for male gender and baseline age, left ventricular ejection fraction and QRS width (HR = 2.8 [1.3-5.8], P = .006). Similarly, new-onset AF predicted ventricular tachyarrhythmias when adjusting for New York Heart Association class ≥ II and baseline QRS width (HR = 2.3 [1.2-4.4], P = .019). After dividing ventricular tachyarrhythmias into subgroups of non-sustained ventricular tachycardia (VT), sustained VT and ventricular fibrillation (VF), new-onset AF was significantly associated with an increased risk of non-sustained- and sustained VT but not VF (non-sustained VT: HR = 3.5 [1.7-7.2], P < .001, sustained VT: HR = 4.2 [1.1-15.7], P = .035, VF: HR = 1.1 [0.2-5.8], P = .877). CONCLUSION: In patients surviving a MI with reduced left ventricular systolic function, new-onset AF is associated with a significantly increased risk of developing ventricular brady- and tachyarrhythmias.

Bloqueo aurículoventricular de alto grado que complica el infarto de miocardio con elevación ST en la era de la intervención coronaria percutánea primaria

Resumen Finalidades: la intervención percutánea coronaria primaria (pPCI, por sus siglas en inglés) ha reemplazado la trombolisis como tratamiento de elección para el infarto de miocardo con elevación del segmento ST (STEMI por sus siglas en inglés). Sin embargo, la incidencia y la importancia pronóstica del bloqueo aurículoventricular de alto grado (BAV-AG) en pacientes con STEMI en la era de pPCI han sido poco estudiadas. El objetivo de este estudio fue evaluar la incidencia, los predictores y la importancia pronóstica of BAV-AG en pacientes con STEMI tratados con pPCI. Métodos y resultados: este estudio incluyó 2073 pacientes con STEMI tratado con pPCI. Los pacientes fueron identificados a través de un registro hospitalario y el Registro Nacional de Pacientes de Dinamarca. Ambos registros se usaron también para establecer el diagnóstico de BAV-AG. La mortalidad por todas las causas fue la variable evaluable primaria. Durante un seguimiento con una mediana de 2,9 años [rango del intercuartil (IQR): 1,8-4,0] fallecieron 266 pacientes. Se documentó bloqueo aurículoventricular de alto grado en 67 (3,2%) pacientes, 25 de los cuales murieron. Entre los predictores independientes importantes de presentar BAV-AG, se incluyeron la oclusión de la arteria coronaria derecha, edad >65 años, género femenino, hipertensión, y diabetes. La tasa de mortalidad ajustada aumentó significativamente en pacientes con BAV-AG comparado con pacientes sin BAV-AG [cociente de riesgos instantáneos » 3,14 (intervalo de confianza 95%: 2,04-4,84), P < 0,001]. Un análisis relevante 30 días después del STEMI mostró iguales tasas de mortalidad en los dos grupos. Conclusión: la incidencia de BAV-AG en pacientes con STEMI tratado con pPCI se ha reducido comparado con los informes de la era trombolítica. Sin embargo, a pesar de esta mejora, en la era de pPCI el bloqueo AV de alto grado sigue siendo un marcador pronóstico severo. La tasa de mortalidad solo aumentó dentro de los primeros 30 días. Los pacientes con bloqueo aurículoventricular de alto grado que sobrevivieron más allá de este punto temporal tuvieron así un pronóstico igual al de los pacientes sin BAV-AG

Summary Aims: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI. Methods and results: This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age .65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P < 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. Conclusion: The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB

High-degree atrioventricular block complicating ST-segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

AIMS: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI. METHODS AND RESULTS: This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age >65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P< 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. CONCLUSION: The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB.

Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma - a single centre's experience.

Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and correlation with pathologic and clinical characteristics, including response to Rituximab-containing chemotherapy and survival, in an unselected cohort of patients with LBCL. Translocations involving BCL2 and MYC loci were examined with fluorescent in situ hybridization (FISH) in 157 patients with diffuse large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). The incidence of DH was 11% in the total cohort, 7% of primary LBCL and 21% of transformed LBCL. DH lymphomas were all GCB immunophenotype and were more often BCLU. No clinical characteristics were correlated with the presence of DH, which also had no impact on overall response rate (ORR), relapse rate or overall survival (OS). However, sub-stratification of DH lymphomas by FISH indicated a possible inferior survival related to immunoglobulin MYC translocation partner gene. Screening of patients with BCLU and DLBCL of GCB type for DH BCL2/MYC translocation including MYC translocation partner gene may provide important prognostic information.

Clinical significance of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction--a Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) substudy.

BACKGROUND: High-degree atrioventricular block (HAVB) is a frequent complication in the acute stages of a myocardial infarction associated with an increased rate of mortality. However, the incidence and clinical significance of HAVB in late convalescent phases of an AMI is largely unknown. The aim of this study was to assess the incidence and prognostic value of late HAVB documented by continuous electrocardiogram (ECG) monitoring in post-AMI patients with reduced left ventricular function. METHODS: The study included 286 patients from the CARISMA study with AMI and left ventricular ejection fraction of 40% or less. An insertable loop recorder was implanted 5 to 21 days after AMI for incessant arrhythmia surveillance. Furthermore, ECG documentation was supplemented by a 24-hour Holter monitoring conducted at week 6 post-AMI. The clinical significance of HAVB occurring more than 21 days after AMI was examined with respect to development of major heart failure events and major ventricular tachyarrhythmic events. RESULTS: During a median follow-up of 1.9 years (interquartile range 0.9-2.0), late HAVB was documented in 30 patients. The risk of major heart failure events (hazard ratio [HR] 4.08 [1.38-12.09], P = .01) and major ventricular tachyarrhythmic events (HR = 5.41 [1.88-15.58], P = .002) were significantly increased in patients who developed late HAVB. CONCLUSION: High-degree atrioventricular block documented by continuous ECG monitoring occurring more than 3 weeks after AMI is a frequent complication in post-AMI patients with left ventricular dysfunction. Furthermore, HAVB is associated with ominous prognostic implications of both potentially lethal arrhythmias and heart failure.

Risk markers of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction: a CARISMA substudy.

AIMS: High-degree atrioventricular block (HAVB) after acute myocardial infarction (AMI) is associated with increased risk of mortality. Risk markers and predictors of HAVB occurring after AMI are largely unknown. The aim of this study was to assess the predictive value of risk markers derived from a series of non-invasive and invasive tests for the development of HAVB documented by an implantable loop recorder (ILR) in late convalescent phases of an AMI. METHODS AND RESULTS: The study included 292 patients with AMI and subsequent left ventricular dysfunction without prior HAVB or implanted pacemaker. An ILR was implanted for continuous arrhythmia surveillance. Risk stratification testing was performed at inclusion and 6 weeks after AMI. The tests included echocardiography, electrocardiogram (ECG), 24 h Holter monitoring, and an invasive electrophysiological study. High-degree atrioventricular block was documented in 28 (10%) patients during a median follow-up of 2.0 (0.4-2.0) years. Heart rate variability (HRV) measures and non-sustained ventricular tachycardia occurring at the week 6 Holter monitoring were highly predictive of HAVB. Power law slope <-1.5 ms(2)/Hz was the most powerful HRV parameter (HR = 6.02 [2.08-17.41], P < 0.001). CONCLUSION: Late HAVB development in post-AMI patients with left ventricular dysfunction can be predicted by risk stratification tests. Measures of HRV reflecting autonomic dysfunction revealed the highest predictive capabilities.

Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study.

BACKGROUND: Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction. METHODS AND RESULTS: A total of 1393 of 5869 patients (24%) screened in the acute phase (3 to 21 days) of an acute myocardial infarction had left ventricular ejection fraction ≤40%. After exclusions, 297 patients (21%) (mean±SD age, 64.0±11.0 years; left ventricular ejection fraction, 31±7%) received an implantable cardiac monitor within 11±5 days of the acute myocardial infarction and were followed up every 3 months for an average of 1.9±0.5 years. Predefined bradyarrhythmias and tachyarrhythmias were recorded in 137 patients (46%); 86% of these were asymptomatic. The implantable cardiac monitor documented a 28% incidence of new-onset atrial fibrillation with fast ventricular response (≥125 bpm), a 13% incidence of nonsustained ventricular tachycardia (≥16 beats), a 10% incidence of high-degree atrioventricular block (≤30 bpm lasting ≥8 seconds), a 7% incidence of sinus bradycardia (≤30 bpm lasting ≥8 seconds), a 5% incidence of sinus arrest (≥5 seconds), a 3% incidence of sustained ventricular tachycardia, and a 3% incidence of ventricular fibrillation. Cox regression analysis with time-dependent covariates revealed that high-degree atrioventricular block was the most powerful predictor of cardiac death (hazard ratio, 6.75; 95% confidence interval, 2.55 to 17.84; P<0.001). CONCLUSIONS: This is the first study to report on long-term cardiac arrhythmias recorded by an implantable loop recorder in patients with left ventricular ejection fraction ≤40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients with depressed left ventricular ejection fraction after acute myocardial infarction. Intermittent high-degree atrioventricular block was associated with a very high risk of cardiac death. Clinical Trial Registration- URL: http://www.ClinicalTrials.gov, Unique identifier: NCT00145119.

Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma.

BACKGROUND: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. METHODS: We conducted a retrospective study of 208 patients treated with HDT. The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. RESULTS: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation related mortality was similar between the groups. CONCLUSION: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because broad-spectrum antibiotic treatment could be initiated immediately. A safe outpatient setting with prophylactic antibiotic treatment is dependent on continuous collection and registration of microbiological findings.